4-Toluenesulfonyl chloride → 2-Chloro-4-fluoro-N-((2R,4R)-3-(2-methyl-piperidin-4-ylamino)-phenyl)-benzamide hydrochloride

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Reaction Steps

Dissolve (2R,4R)-4-(3-(2-chloro-4-fluoro-benzoylamino)-phenylamino)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester (Preparation 59, 119 mg, 0.258 mmol) in toluene (5 mL). Add p-toluenesulfonyl chloride (152 mg, 0.798 mmol) and heat to 100° C. for 3 hr. Cool to room temperature and load onto an SCX column with methanol. Wash the column with methanol, flush with 2M ammonia in methanol, and concentrate in vacuo. Purify by column chromatography (0%–10% 2M NH3 in methanol/CH2Cl2) to yield an oil. Make the hydrochloride salt by sonication with one equivalent of ammonium chloride dissolved in methanol to yield 40 mg (39%) of the title compound: mass spectrum (ion spray): m/z=362.1 (M+1); 1H NMR δ (D2O/DCl, ppm) 7.78 (s, 1H), 7.49 (m, 3H), 7.21 (t, J=9.0 Hz, 18.0 Hz, 2H), 7.07 (t, J=9.0 Hz, 18.0 Hz, 1H), 3.83 (m, 1H), 3.45 (m, 1H), 3.20 (m, 1H), 2.95 (m, 1H), 2.18 (m, 2H), 1.80 (m, 1H), 1.65 (m, 1H), 1.20 (d, J=6.6 Hz, 3H); mp 182–5° C.

Provenance & Evidence